Provigil (Modafinil) Treatment and Dosing Recommendations
Primary Recommendation
For FDA-approved indications (narcolepsy, obstructive sleep apnea, shift work disorder), start with 200 mg once daily in the morning, with a maximum dose of 400 mg per day. 1
FDA-Approved Indications
Modafinil is approved to improve wakefulness in three specific conditions: 1
- Narcolepsy: 200 mg once daily in the morning 1
- Obstructive Sleep Apnea (OSA): 200 mg once daily in the morning as adjunct therapy (not a treatment for the underlying airway obstruction) 1
- Shift Work Disorder (SWD): 200 mg once daily, taken approximately one hour prior to start of work shift 1
Dosing Algorithm by Clinical Scenario
Standard Dosing for Sleep Disorders
- Initial dose: 200 mg once daily 1
- Maximum dose: 400 mg per day (single morning dose or divided into morning and midday doses) 2
- Timing: Last dose should be no later than 2:00 PM to avoid insomnia 2
Cancer-Related Fatigue (Off-Label)
For predominantly cognitive symptoms and fatigue: 2, 3
- Start with 100 mg once daily in the morning 3
- Assess response after 1 week 3
- Increase to 200 mg daily if inadequate response and no side effects 3
- Lower doses (50-200 mg/day) are more appropriate for concentration problems and fatigue 2
For predominantly excessive sleepiness: 2
Special Populations
- Start with 100 mg once upon awakening 2
- Increase at weekly intervals as necessary 2
- Consider lower doses than standard recommendations 1
Severe Hepatic Impairment: 1
- Reduce dose to half the recommended dose 1
Critical Safety Warnings
Life-Threatening Reactions
- Stevens-Johnson Syndrome: Discontinue immediately at first sign of rash unless clearly not drug-related 2, 1
- Risk is particularly elevated in pediatric patients - modafinil is NOT FDA-approved for patients under 17 years 2
- Angioedema and anaphylaxis: Discontinue if suspected 1
- Multi-organ hypersensitivity reactions: Discontinue if suspected 1
Cardiovascular Monitoring
- Monitor blood pressure and heart rate, especially in patients with known cardiovascular disease 4, 1
- Screen for cardiovascular contraindications before initiating therapy 4
- Contraindicated in moderate to severe hypertension 5
Psychiatric Considerations
- Use caution in patients with history of psychosis, depression, or mania 1
- Monitor for development of psychiatric symptoms and consider discontinuation if they occur 1
Common Adverse Effects
The most frequently reported side effects (≥5%) include: 1
- Headache (most common, reported in 34% vs 23% placebo) 6
- Nausea 1, 6
- Nervousness 2, 1
- Back pain 2
- Insomnia 2, 1
- Anxiety 1
- Dyspepsia 2, 1
Expected Timeline for Response
For cancer-related fatigue: 3
- Significant reduction expected by week 2 (46% of patients show improvement) 3
- Peak effect by week 4 (75% of responders show benefit) 3
Important Drug Interactions and Contraindications
Contraceptive Efficacy
- Modafinil reduces effectiveness of oral contraceptives 4, 5
- Use alternative or concomitant contraception methods during treatment and for one month after discontinuation 1
Other Significant Interactions
- Cyclosporine: Blood concentrations may be reduced 1
- CYP2C19 substrates (omeprazole, phenytoin, diazepam): Exposure may be increased 1
Pregnancy and Lactation
- May cause fetal harm based on animal data 4, 1
- 2018 pregnancy registry showed higher rates of major congenital anomalies with in utero exposure 4
- Avoid during pregnancy and breastfeeding 4
Abuse Potential and Withdrawal
- Lower abuse potential than traditional stimulants (amphetamines, methylphenidate) 2, 3
- Minimal withdrawal phenomena 3
- Lacks rapid onset behavioral effects that cause anxiety 3
- Classified as Schedule IV controlled substance 1
Pharmacokinetic Properties
- Half-life: Approximately 15 hours 2
- Steady state: Reached after 2-4 days of dosing 2
- Peak plasma concentration: 2.3 hours after oral dose 5
- Extensively metabolized in liver to inactive metabolites 5
Monitoring Parameters
Monitor during first 2 weeks and ongoing: 3